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Reproductive outcomes of women aged 40 and older undergoing IVF with donor sperm

December 2020
Human Reproduction 36(1)

Authors:

Reproductive Medicine Associates of New York

STUDY QUESTION Do women ≥40 years old without a male partner who utilize donor sperm have the same reproductive outcomes as those who utilize their partner’s sperm? SUMMARY ANSWER After controlling for relevant confounders, women ≥40 years old using donor sperm for IVF have significantly higher odds of having a live birth compared to those utilizing their partner’s sperm. WHAT IS KNOWN ALREADY Women who are unpartnered or in same-sex relationships are by definition not infertile, but may choose to conceive using donor sperm. It is not known how IVF outcomes are affected with the use of donor sperm compared to women utilizing their partner’s sperm, particularly at very advanced maternal ages. STUDY DESIGN, SIZE, DURATION This is a retrospective cohort study conducted at a university-affiliated center of women undergoing IVF with fresh embryo transfer between 2008 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients were divided into two groups based on the ejaculated sperm source utilized: donor or partner sperm. Live birth rate was the primary outcome. Pregnancy rate was the secondary outcome. Multivariable logistic regression was performed and adjusted for age, the developmental stage of the embryo, and the number of embryos transferred. Unadjusted odds ratio (OR) and adjusted OR (aOR) with 95% CI for pregnancy and live birth were estimated. Statistical significance was denoted by P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE A total of 3910 cycles in women ≥40 years old were analyzed, of which 307 utilized donor sperm and 3603 utilized their partner’s sperm to conceive. In the univariate analysis, patients utilizing donor sperm were found to have similar pregnancy rates as those utilizing partner sperm (41.0 vs 39.8%, OR: 0.95, 95% CI: 0.75–1.20). After adjusting for age, the number of embryos transferred and the developmental stage of the embryos, the model estimates did not vary (aOR: 1.22, 95% CI: 0.95–1.56). Similarly, the univariate analysis for live birth did not demonstrate a difference between groups (19.2 vs 17.8%, OR: 0.91, 95% CI: 0.67–1.22). However, after a similar adjustment was made for confounders, the use of donor sperm was associated with statistically significant increased odds of live birth (aOR: 1.38, 95% CI: 1.01–1.88). LIMITATIONS, REASONS FOR CAUTION As with any retrospective study, the potential for residual confounding exists, despite attempts to control for this with regression modeling. WIDER IMPLICATIONS OF THE FINDINGS Women ≥40 years old who are unpartnered or in same-sex relationships can be counseled that their odds of a live birth are slightly better than women in heterosexual relationships utilizing their partner’s sperm. These findings serve to further refine and individualize counseling on the expected IVF outcomes for women in this population. STUDY FUNDING/COMPETING INTEREST(S) No funding was sought for this study. The authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A.

Pregnancy rate by age group categorized by partner (blue) versus donor (red) sperm.

…

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Reproductive outcomes of women

aged 40 and older undergoing IVF

with donor sperm

P. Bortoletto

*, S. Willson

, P.A. Romanski

, O.K. Davis

, and

Z. Rosenwaks

The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, NY, USA

Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA

*Correspondence address. The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, 1305 York Avenue, 6th Floor,

New York, NY 10021, USA. Tel: þ1-646-962-2764; E-mail: pib9008@med.cornell.edu

Submitted on July 4, 2020; resubmitted on September 21, 2020; editorial decision on September 27, 2020

STUDY QUESTION: Do women 40 years old without a male partner who utilize donor sperm have the same reproductive outcomes

as those who utilize their partner’s sperm?

SUMMARY ANSWER: After controlling for relevant confounders, women 40 years old using donor sperm for IVF have signiﬁcantly

higher odds of having a live birth compared to those utilizing their partner’s sperm.

WHAT IS KNOWN ALREADY: Women who are unpartnered or in same-sex relationships are by deﬁnition not infertile, but may

choose to conceive using donor sperm. It is not known how IVF outcomes are affected with the use of donor sperm compared to women

utilizing their partner’s sperm, particularly at very advanced maternal ages.

STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study conducted at a university-afﬁliated center of women under-

going IVF with fresh embryo transfer between 2008 and 2018.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were divided into two groups based on the ejaculated sperm source

utilized: donor or partner sperm. Live birth rate was the primary outcome. Pregnancy rate was the secondary outcome. Multivariable logis-

tic regression was performed and adjusted for age, the developmental stage of the embryo, and the number of embryos transferred.

Unadjusted odds ratio (OR) and adjusted OR (aOR) with 95% CI for pregnancy and live birth were estimated. Statistical signiﬁcance was

denoted by P<0.05.

MAIN RESULTS AND THE ROLE OF CHANCE: A total of 3910 cycles in women 40 years old were analyzed, of which 307 utilized

donor sperm and 3603 utilized their partner’s sperm to conceive. In the univariate analysis, patients utilizing donor sperm were found to

have similar pregnancy rates as those utilizing partner sperm (41.0 vs 39.8%, OR: 0.95, 95% CI: 0.75–1.20). After adjusting for age,

the number of embryos transferred and the developmental stage of the embryos, the model estimates did not vary (aOR: 1.22, 95%

CI: 0.95–1.56). Similarly, the univariate analysis for live birth did not demonstrate a difference between groups (19.2 vs 17.8%, OR: 0.91,

95% CI: 0.67–1.22). However, after a similar adjustment was made for confounders, the use of donor sperm was associated with

statistically signiﬁcant increased odds of live birth (aOR: 1.38, 95% CI: 1.01–1.88).

LIMITATIONS, REASONS FOR CAUTION: As with any retrospective study, the potential for residual confounding exists, despite

attempts to control for this with regression modeling.

WIDER IMPLICATIONS OF THE FINDINGS: Women 40 years old who are unpartnered or in same-sex relationships can be

counseled that their odds of a live birth are slightly better than women in heterosexual relationships utilizing their partner’s sperm. These

ﬁndings serve to further reﬁne and individualize counseling on the expected IVF outcomes for women in this population.

STUDY FUNDING/COMPETING INTEREST(S): No funding was sought for this study. The authors declare no competing interests.

TRIAL REGISTRATION NUMBER: N/A.

Key words: advanced maternal age / donor sperm / IVF / outcomes / fresh embryo transfer

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Human Reproduction, Vol.36, No.1, pp. 229–235, 2021

Advance Access Publication on December 2, 2020 doi:10.1093/humrep/deaa286

ORIGINAL ARTICLE Reproductive epidemiology

Downloaded from https://academic.oup.com/humrep/article/36/1/229/6017141 by guest on 08 October 2023

Introduction

In the USA, the average maternal age at first birth has been steadily

rising, with an increasing proportion of women conceiving between

the ages of 30 and 44 years old (Martin et al.,2018). Although many

women seek treatment for subfertility in advanced maternal age, there

is a decrease in the success rates of fertility treatments in this group.

Among all women above the age of 40 in the USA who underwent

IVF between 2007 and 2013, the live birth rate among IVF cycles

resulting in transfer was only 16.1% (Hipp et al.,2017). Additionally,

the latest Society for Assisted Reproductive Technology (SART)

National Summary Report shows that the likelihood of pregnancy loss

after ART increases with age: 12.9% for women younger than 35 years

of age, 15.2% for those 35–37years of age, 19.8% for those

38–40 years of age and 26.8% for those older than 40 years of age

(SART, 2017).

However, studies examining pregnancy and miscarriage rates are

largely based on populations consisting of women seeking ART in the

setting of a pre-existing diagnosis of infertility. Not all women of ad-

vanced reproductive age who wish to conceive are by definition infer-

tile, including those in same-sex couples and unpartnered women who

seek ART services for family building. De Brucker et al. (2009) have

demonstrated that cumulative delivery rates with IUI using donor

sperm decreased with maternal age, despite the primary indication for

treatment (heterosexual couples with severe male factor infertility, sin-

gle parent request, and same-sex couples). A study comparing fertility

outcomes in same-sex versus heterosexual couples undergoing IUI

with donor sperm showed no significant difference in the pregnancy or

overall live birth rates (Nordqvist et al., 2014). Importantly, the oldest

woman included in this study was 39 years old. A separate study com-

paring same-sex or unpartnered women undergoing ovulation induc-

tion/IUI to heterosexual couples with any infertility diagnosis also

found that both groups had similar pregnancy outcomes (Nazem et al.,

2017). In this study, it was not specified whether the heterosexual

couples were seeking ART due to male factor, female factor or unex-

plained infertility. There are no published studies assessing the repro-

ductive outcomes of unpartnered or same-sex women 40 years old

who utilize donor sperm and IVF to conceive.

Providing an accurate estimate of ART success rates for women in

this unique clinical and social scenario is key to counseling patients on

their likelihood of IVF treatment success. The purpose of this study is

to compare the pregnancy and live birth rates of women in this ad-

vanced age group undergoing IVF without a male partner who utilize

donor sperm to those who utilize their partner’s sperm.

Materials and methods

Study population and design

All patients undergoing controlled ovarian hyperstimulation (COH) be-

tween 1 January 2008 and 31 December 2018, at the Ronald O.

Perelman and Claudia Cohen Center for Reproductive Medicine were

reviewed. We included women aged 40 years and older undergoing

their first COH cycle at our center followed by a fresh cleavage (Day

3) or blastocyst (Day 5) embryo transfer (ET). We excluded women

who had previously undergone more than six IUI cycles at our center

(n ¼59) and those utilizing non-ejaculated sperm (i.e. TESE, epididymal

sperm extraction or percutaneous aspiration) (n ¼129).

Definition of study groups

A total of 3910 patients met inclusion criteria and were stratified into

two groups based on the primary sperm source: donor sperm

(n ¼307) and partner sperm (n ¼3603). For the cohort of women

utilizing donor sperm, we excluded those with a male partner in order

to identify only unpartnered women or those in same-sex relation-

ships. Women utilizing donor sperm despite having a male partner

were excluded as we wanted to focus, as best we can, on women

whom have not previously been exposed to an opportunity to

become pregnant. In the case of non-obstructive azoospermia, for

example, several etiologies can be progressive (i.e. varicocele,

medication-induced, exposure to toxins/radiations/surgery) and may

have resulted in past exposure to ejaculate and therefore an opportu-

nity at conception.

Clinical protocols

Patients underwent COH with a flexible GnRH antagonist or agonist

protocol with the protocol and dose determined according to patient

age, weight, ovarian reserve and prior response to stimulation (Surrey

et al., 1998;Cheung et al.,2005). Patients with diminished ovarian re-

serve received hormone priming in the mid-luteal phase of the cycle

prior to the ovarian stimulation cycle, and either 0.1 mg estradiol

patches (Climara 0.1 mg, Bayer HealthCare) or oral contraceptive pills

(Ortho-Novum, Janssen Pharmaceuticals) were administered (Dragisic

et al., 2005). Ovulation was triggered with either an hCG (Novarel

(Ferring Pharmaceuticals Inc., Parsippany, NJ, USA) or Pregnyl (Merck,

Whitehouse Station, NJ, USA)) trigger, or a dual trigger with hCG and

GnRH agonist (leuprolide acetate) with hCG dosing based on a

sliding-scale regimen (Pereira et al., 2015,2016). Oocyte retrieval was

performed under conscious sedation using transvaginal ultrasound

guidance approximately 35–37h after ovulatory trigger. At our center,

all women utilizing frozen donor sperm to conceive undergo ICSI.

Embryos were evaluated on the morning of Day 3 and Day 5 depend-

ing on embryonic development and were graded according to a

method previously described (Veeck, 1999).

The day of ET and the number of embryos to transfer were deter-

mined by the treating physician in consultation with the embryologist

and patient. ET was performed using a Wallace catheter (Smiths

Medical, Norwell, MA). Ultrasound guidance for ET was utilized at the

discretion of the treating physician. It should be noted that all patients

undergo a trial transfer prior to their cycle start to identify patients

who would benefit from ultrasound guidance. All patients received

daily intramuscular progesterone (50mg) beginning the day after oo-

cyte retrieval until 8–10 weeks gestation. Patients receiving a dual trig-

ger were also placed on estradiol transdermal patches (0.1 mg) every

other day until 8–10weeks gestation. A serum hCG test was per-

formed 10 days following ET, followed by transvaginal ultrasound to

confirm intrauterine pregnancy by 5.5–7 weeks of gestation.

Demographics and outcomes

The primary outcome of this study was live birth rate, defined as the

delivery of a viable infant after 24 weeks of gestation. The secondary

230 Bortoletto et al.

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outcome was pregnancy rate, defined as a positive serum hCG test.

Biochemical pregnancy was defined as detection of beta hCG in serum

or urine which then self-resolved prior to sonographic detection of in-

trauterine pregnancy. Miscarriage was defined as loss of clinical preg-

nancy before 24 weeks gestation. Parametric and non-parametric

descriptive statistics were utilized to examine differences between the

groups.

Statistical analysis

A multivariable logistic regression analysis was conducted to identify

variables independently associated with our primary and secondary

outcomes, in addition to biochemical pregnancy and miscarriage. The

primary exposure was the sperm source utilized: donor versus partner

sperm. The following covariates were identified as important to con-

trol for a priori: age (40–41 vs 42 and older), the number of embryos

transferred (less than or equal to 3 vs 4 or more) and the develop-

mental stage of the embryo at the time of transfer (blastocyst vs cleav-

age). A sub-group analysis was also performed whereby patients in the

partner sperm group were excluded if male-factor or idiopathic infertil-

ity were identified. Odds ratios (ORs) and adjusted ORs (aORs) are

reported with 95% CI. Data analysis was performed using STATA SE

version 16 (StataCorp LP).

Ethical approval

This study was approved by the Weill Cornell Medical College

Institutional Review Board study protocol number 19-04020098.

Results

In total, 3910 patients met inclusion criteria, of which 307 utilized do-

nor sperm and 3603 utilized their partner’s sperm to conceive. Those

utilizing donor sperm were older (42.3 vs 41.7), less gravid (0 vs 1

previous pregnancy) and less likely to have a concurrent diagnosis of

female factor infertility. Both groups had comparable anti-Mullerian

hormone (AMH) levels (1.26 vs 1.28ng/ml). Patient characteristics for

our cohort are displayed in Table I, and cycle characteristics are shown

in Table II. Cycle outcomes with univariate odds ratios are displayed in

Table III.

Live birth

In the univariate analysis, patients utilizing donor sperm were found to

have similar live birth rates as those utilizing their partner’s sperm

(19.2 vs 17.8%, OR: 0.91, 95% CI: 0.67–1.22). After adjusting for age,

the number of embryos transferred, and the developmental stage of

the embryos, the use of donor sperm was associated with statistically

significant increased odds of live birth (aOR: 1.38, 95% CI: 1.01–1.88).

Patients 42 and older were significantly less likely to have a live birth

(aOR: 0.34, 95% CI: 0.28–0.40) compared to those aged 40 to 41.

The transfer of four or more embryos (aOR: 2.22, 95% CI: 1.82–

2.66) and the transfer of blastocyst-stage embryos (aOR: 2.53, 95%

CI: 1.90–3.36) were both associated with increased odds of live birth

compared to the transfer of three or fewer embryos or the transfer of

cleavage-stage embryos (see Table IV). Figure 1 displays the live birth

rate per age group, stratified by partner versus donor sperm. There

was a statistically significant linear trend toward lower live birth rates

with advancing age (P<0.001).

Pregnancy

Pregnancy and live birth rates are reported in Table III. In the univari-

ate analysis, patients utilizing donor sperm were found to have similar

pregnancy rates as those utilizing their partner’s sperm (41.0 vs 39.8%,

OR: 0.95, 95% CI: 0.75–1.20). After adjusting for age, the number of

embryos transferred, and the developmental stage of the embryos,

the model estimates did not vary (aOR: 1.22, 95% CI: 0.95–1.56).

Patients 42 and older were significantly less likely to become pregnant

(aOR: 0.49, 95% CI: 0.42–0.56) compared to those aged 40–41.

Transfer of four or more embryos (aOR: 2.31, 95% CI: 2.01–2.66)

and transfer of blastocyst-stage embryos (aOR: 2.57, 95% CI: 2.01–

3.29) were both associated with increased odds of becoming pregnant

compared to the transfer of three or fewer embryos or the transfer of

cleavage-stage embryos (see Table IV). Figure 2 displays the pregnancy

rate per age group, stratified by partner versus donor sperm. There

was a statistically significant linear trend toward lower pregnancy rates

with advancing age (P<0.001).

A multivariate analysis for biochemical pregnancy and miscarriage

was also performed. After adjustment for the same covariates of inter-

est as above, the odds of biochemical pregnancy (aOR: 1.16, 95% CI:

0.78–1.72) and miscarriage (aOR: 0.81, 95% CI: 0.56–1.17) were not

different if using donor versus partner sperm to conceive (see

Table IV). A subgroup analysis was then performed whereby patients

............................................ ............................................ ..............

Table I Patient characteristics.

Donor

sperm

Partner

sperm

n5307 n 53603

Age (years), mean (SD) 42.3 (1.7) 41.7 (1.6)

Gravidity, median (IQR) 0 (0–1) 1 (0–2)

Parity, median (IQR) 0 (0–0) 0 (0–1)

BMI (kg/m

), mean (SD) 24.3 (7.6) 23.6 (6.5)

Ethnicity, n (%)

Unknown/other 127 (41.2) 1767 (48.9)

White 168 (54.6) 1394 (38.6)

Asian 13 (4.2) 452 (12.5)

Infertility diagnosis, n (%)

Idiopathic 2 (0.7) 30 (0.8)

Immunologic 0 (0.0) 1 (0.03)

Male factor 0 (0.0) 712 (19.7)

Tubal factor 29 (9.4) 599 (16.6)

Anovulatory 3 (1.0) 65 (1.8)

Endometriosis 14 (4.6) 325 (9.0)

Uterine factor 27 (8.8) 261 (7.2)

Diminished ovarian reserve 271 (88.0) 2897 (80.2)

AMH level (ng/ml), mean (SD) 1.26 (1.9) 1.28 (1.4)

Previous IUI cycles, median (IQR) 3 (2–4) 2 (1–3)

Previous IVF cycles elsewhere, median (IQR) 2 (1–3) 2 (1–3)

AMH, anti-Mullerian hormone; IQR, interquartile range.

Donor sperm in women over 40 231

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utilizing their partners sperm who had been diagnosed with male-factor

or idiopathic infertility were excluded (n ¼739). The adjusted odds of

achieving a pregnancy (aOR: 1.29, 95% CI: 1.00–1.68, P¼0.048)anda

live birth (aOR: 1.47, 95% CI: 1.08–2.02, P¼0.015)werelargely

unchanged by the exclusion of these patients. The results of the unad-

justed and adjusted analysis are presented in Supplementary Table SI.

Finally, given the 10-year time span of the study and our centers

changing practice patterns, an additional regression model was under-

taken to account for time of IVF cycle (early: 2008–2010, middle:

2011–2015 and late: 2016–2018) as well as the utilization of ultra-

sound guidance (yes vs no) at time of ET. The addition of both of

these covariates did not alter the model estimates for neither the pri-

mary nor secondary outcome.

Discussion

In our study, after controlling for relevant confounders, we found that

women aged 40years or older using donor sperm for IVF have signifi-

cantly higher odds of having a live birth compared to those utilizing

their partner’s sperm.

There are several potential explanations for this unique finding.

Women who are unpartnered or in same-sex relationships have pre-

sumably not had the opportunity to spontaneously conceive and may

not in fact be ‘infertile’. In our cohort of women 40 years old, those

utilizing donor sperm were less likely to have a co-existent female fac-

tor diagnosis, such as tubal factor, endometriosis or anovulation (see

Table I). While women in the donor sperm group were slightly older

than those in the partner sperm group (42.3 vs 41.7, P<0.001), they

had similar ovarian reserve parameters: AMH (1.26 vs 1.28 ng/ml,

P¼0.87), Day-3 estradiol (74.6 vs 78.5 mIU/ml, P¼0.35) and FSH

(4.9 vs 4.8, P¼0.85). As such, the number of mature oocytes re-

trieved was similar between groups (5 vs 6, P¼0.068) as was the

number of embryos transferred (3 vs 3, P¼0.25), giving both groups

a similar opportunity at achieving a pregnancy.

In our multivariate model, the odds of achieving a pregnancy were

similar between women using partner versus donor sperm (aOR:

1.22, 95% CI: 0.95–1.56). The rates of biochemical pregnancy (10.9 vs

9.5, P¼0.421)andmiscarriage(9.9vs11.7,P¼0.302) between

those conceiving with partner versus donor sperm were similar. This

relationship was maintained after multivariate adjustment for both bio-

chemical pregnancy (aOR: 1.16, 95% CI: 0.78–1.72) and miscarriage

(aOR: 0.81, 95% CI: 0.56–1.17). The only cycle outcome that was sig-

nificant more likely for woman utilizing donor sperm was livebirth

(aOR: 1.38, 95% CI: 1.01–1.88). Odds of live birth were higher if

.......................................... ............................................ ................

Table II Cycle characteristics.

Donor sperm Partner sperm

n5307 n 53603

Protocol type, n (%)

GnRH antagonist 236 (77) 2575 (71)

Clomid or letrozole þantagonist 20 (7) 296 (8)

GnRH agonist 51 (17) 732 (20)

Days of stimulation, median (IQR) 10 (9–12) 10 (9–12)

Total gonadotropin dose (IU), mean

(SD)

4574.7 (1775.7) 4384.4 (1836.7)

Cycle start FSH (mIU/ml), mean (SD) 4.9 (3.1) 4.4 (3.1)

Cycle start E2 (pg/ml), mean (SD) 74.59 (58.6) 78.49 (70.2)

Trigger type, n (%)

HCG only 276 (89.9) 3330 (92.4)

Lupron only 2 (0.7) 10 (0.3)

Dual trigger 22 (7.2) 244 (6.8)

Ovidrel 7 (2.3) 19 (0.5)

Number of oocytes retrieved, median

(IQR)

7 (4–11) 7 (5–11)

Number of mature oocytes retrieved,

median (IQR)

5 (4–9) 6 (4–9)

ICSI, n (%) 306 (100) 2688 (75)

Fertilization rate, mean (SD) 79.7 (19.6) 74.7 (21.5)

Number of embryos transferred,

median (IQR)

3 (2–4) 3 (2–4)

Developmental stage of embryo at

time of transfer, n (%)

Cleavage stage 287 (93%) 3316 (92%)

Blastocyst stage 20 (7%) 287 (8%)

................................................................................................................................................................................................. ...........................

Table III Cycle outcomes.

Donor sperm Partner sperm Univariate P-value

n5307 n 53603 OR (95% CI)

n(%)n(%)––

Not pregnant 181 (59.0) 2170 (60.2) 0.95 (0.75–1.20) 0.663

Biochemical pregnancy 29 (9.5) 394 (10.9) 0.85 (0.57–1.26) 0.421

Miscarriage 36 (11.7) 356 (9.9) 1.21 (0.84–1.74) 0.302

Ectopic pregnancy 2 (0.7) 24 (0.7) 0.98 (0.23–4.16) 0.976

Termination 0 (0) 16 (0.4) – –

Still birth 0 (0) 3 (0.8) – –

Live birth 59 (19.2) 640 (17.8) 0.91 (0.68–1.22) 0.523

OR, odds ratio.

232 Bortoletto et al.

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women transferred four or more embryos or transferred blastocysts.

Age 42 and older was associated with a reduction in odds of live birth

compared to women 40 and 41 years of age. Figure 1 demonstrates

this finding and highlights that although the live birth rate is higher in

women conceiving with donor sperm at age 40, the live birth rates are

quite similar at age 42 and beyond.

As the number of women who are unpartnered or in same-sex re-

lationship accessing ART continues to grow, it is important to under-

stand how different treatment options may impact their chances of

achieving a live birth. Ferrara et al. (2000) have previously reported

the outcomes of single and lesbian women undergoing IUI with donor

sperm. They found that the pregnancy rates were similar between

Table IV Multivariate logistic regression.

Pregnant Biochemical pregnancy Miscarriage Livebirth

aOR (95% CI) P-value aOR (95% CI) P-value aOR (95% CI) P-value aOR (95% CI) P-value

Age (years)

40–41 Referent Referent Referent Referent

42 and older 0.49 (0.42–0.56) <0.001 1.10 (0.90–1.35) 0.352 1.07 (0.87–1.33) 0.516 0.34 (0.28–0.40) <0.001

Number of embryos transferred

Less than or equal to 3 Referent Referent Referent Referent

4 or more 2.31 (2.01–2.66) <0.001 0.77 (0.63–0.95) 0.017 0.58 (0.46–0.72) <0.001 2.22 (1.86–2.66) <0.001

Developmental stage of embryo

Cleavage Referent Referent Referent Referent

Blastocyst 2.57 (2.01–3.29) <0.001 0.92 (0.62–1.35) 0.662 0.54 (0.38–0.79) 0.001 2.53 (1.90–3.36) <0.001

Sperm source

Partner Referent Referent Referent Referent

Donor 1.22 (0.95–1.56) 0.114 1.16 (0.78–1.72) 0.472 0.81 (0.56–1.17) 0.260 1.38 (1.01–1.88) <0.040

OR, adjusted odds ratio.

Figure 1. Live birth rate by age group categorized by partner (blue) versus donor (red) sperm.

Donor sperm in women over 40 233

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groups but that lesbian women are more likely to conceive if under

the age of 35. A follow-up study by the same group analyzed over

1000 treatment cycles of both lesbian women and heterosexual

couples utilizing donor IUI. They found that age was the only factor

associated with reduced pregnancy rates in this cohort: 18.5% for

women <35 years, 11.9% in women 35–40years and 5.4% in women

>40 years (P<0.05) (Ferrara et al., 2002). Importantly, there were no

differences in pregnancy rates per cycle between lesbian and hetero-

sexual couples when adjusting for age. Advanced maternal age, and its

associated decline in ovarian reserve, is a common indication for IVF.

A 2014 study by Nordqvist et al. (2014) of lesbian and heterosexual

women undergoing IUI or IVF with donor sperm found that IVF with

donor sperm provided higher live birth rates for lesbian women as

compared to IUI with donor sperm (26 vs 16%). Our study takes this

a step further and specifically focuses on fresh IVF outcomes in women

40 and older who are unpartnered or in same-sex relationships. Live

birth rates in our cohort were 19.2% for those utilizing donor sperm

and 17.8% for women using partner sperm. It is worth noting, how-

ever, that women utilizing donor sperm had a median of 3 (interquar-

tile range: 2–4) IUI cycles preceding their IVF cycle at our center.

The difference in the live birth rate may be accounted for, individu-

ally or in combination, by the source of the sperm or the absence of

coexisting female factor(s) other than age. Men of advanced reproduc-

tive age are known to have significantly higher rates of DNA fragmen-

tation that contributes to higher aneuploidy rates in embryos,

particularly trisomy 21, 18 or 13, compared to men in their 30s

(P<0.05) (Garcı´a-Ferreyra et al., 2018). In the cohort of women utiliz-

ing their partner’s sperm, the mean (SD) age was 43.1 (5.9) and

19.7% carried a diagnosis of male factor infertility. This is compared to

the population of male sperm donors, which is generally much younger

and does not typically have a concurrent diagnosis of male factor infer-

tility (Freeman et al., 2016). Importantly, in our sub-group analysis, ex-

cluding patients utilizing donor sperm with a male-factor or idiopathic

infertility diagnosis did not change the results of our primary outcome

(aOR: 1.47, 95% CI: 1.08–2.02). Lastly, the advanced paternal age

encountered in the partner sperm group has been associated with

increased odds of spontaneous abortion, independent of maternal age

(Nguyen et al.,2019). However, in our study, the odds of miscarriage

were similar between women utilizing donor versus partner sperm

(aOR: 0.81, 95% CI: 0.56–1.17) (see Table IV).

Our study has several strengths. Our patient sample for analysis

within this age group is uniquely large in size. Additionally, women with

previous failed blastocyst transfers are referred to our center due to our

experience with Day-3 fresh ET. As such, it is possible that the preg-

nancy and live birth rates in a similar cohort at other centers may be

even higher than those we report. Our study is not without its

limitations. First, we chose to exclude women who had previously

undergonemorethansixIUIcycles.Exclusion of this group may bias

results, as this is likely a cohort of women less likely to achieve a preg-

nancy or live birth via IVF. However, this only comprised a total of

65 patients in our dataset. Secondly, we only assessed the outcomes of

fresh ETs and did not extend our study to analyze cumulative pregnancy

rates with supernumerary, cryopreserved embryos. We commonly per-

form fresh Day-3 transfer in older patients with few available embryos

so as to mitigate the risks of attrition. Third, our center routinely per-

forms ICSI for non-male factor infertility as represented by a 75% ICSI

rate in our population using their partners sperm. Reasons for this

include history of prior poor fertilization, success with prior ICSI cycle or

patient/provider preference. While we do not feel this affected our pri-

mary or secondary outcomes, careful extrapolation to other centers us-

ing conventional insemination is warranted.Finally,oureffortstoexclude

womenwithmalepartnerslinkedtotheir electronic medical records

may have inadvertently excluded patients, although we suspect the likeli-

hood of this is low given the robust registration process at our center.

In conclusion, after controlling for relevant confounders, we ob-

served that women aged 40years or older using donor sperm for IVF

have significantly higher odds of having a live birth compared to those

utilizing their partner’s sperm. These findings may serve to further re-

fine and individualize counseling on the expected IVF outcomes for

women in this demographic.

Figure 2. Pregnancy rate by age group categorized by partner (blue) versus donor (red) sperm.

234 Bortoletto et al.

Downloaded from https://academic.oup.com/humrep/article/36/1/229/6017141 by guest on 08 October 2023

Supplementary data

Supplementary data are available at Human Reproduction online.

Data availability

The data underlying this article will be shared on reasonable request

to the corresponding author.

Acknowledgements

We would like to thank Alexandra MacWade for her help in proof-

reading the manuscript.

Authors’ roles

P.B.: participated in study design, execution, analysis planning, manu-

script drafting and editing. S.W.: participated in study design, analysis

planning, manuscript drafting and editing. P.A.R.: participated in study

design, analysis planning, manuscript drafting and editing. O.D.: partici-

pated in study design, analysis planning and manuscript editing. Z.R.:

participated in study design, analysis planning and manuscript editing.

Funding

No financial support, funding or services were obtained for this study.

Conflict of interest

The authors do not have any conflict of interest disclosures.

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Beyond the egg: sperm source does not impact cumulative live birth rates in autologous oocyte cryopreservation patients when adjusted for oocyte age

Article

Full-text available

Nov 2024
J ASSIST REPROD GEN

Purpose To assess the impact of sperm source on cumulative live birth rate (CLBR) after oocyte thaw in autologous oocyte cryopreservation (AOC) patients. Methods A retrospective cohort study of autologous oocyte thaw patients at an urban academic fertility center from 2006 to 2021. Patients were stratified by sperm source [partner sperm (PS) vs. donor sperm (DS)]. The primary outcome was CLBR per patient. Secondary outcomes were the oocyte survival rate and usable embryo rate. Statistics included Mann–Whitney U, Kruskal–Wallis, Fisher’s exact, chi-square, two-sample t-tests, and multiple logistic regression (p < 0.05). Results A total of 653 patients were included; 455 (69.7%) used PS and 198 (30.3%) used DS. Time from the first AOC to the first thaw did not differ among DS and PS users (56.8 vs. 54.0 months, p = 0.20). PS users were younger at AOC (37.9 vs. 38.5 years, p < 0.001) and thaw (42.3 vs. 43.1 years, p < 0.001). There were equivalent overall CLBRs (39.9% PS vs. 40.6% DS, p = 0.85) and CLBRs in patients < 35 years at AOC (51.2% PS vs. 100% DS, p = 0.18), 35–37 years at AOC (45.9% PS vs. 60.4% DS, p = 0.10), 38–40 years at AOC (35.4% PS vs. 35.2% DS, p = 0.93), 41–42 years at AOC (28.9% PS vs 14.3% DS, p = 0.21), and > 43 years at AOC (12.5% PS vs 16.7% DS, p = 0.83) among PS and DS users. There were no significant differences in the oocyte survival (79% PS vs 80.5% DS, p = 0.08) or the proportion of patients with usable embryos (27.3% vs 27.8%, p = 0.70) between PS and DS groups. Conclusions In AOC patients, CLBR, oocyte survival rate, and usable embryo rate did not differ based on sperm source.

Cumulative live birth rates following intrauterine insemination using donor and husband sperm in different age groups: A cohort study of 10 415 insemination cycles

Article

Full-text available

Apr 2024
INT J GYNECOL OBSTET

Objectives To assess the age‐specific cumulative live birth rates (CLBRs) in intrauterine insemination (IUI) cycles using either donor or husband sperm, and to investigate the impact of sperm sources on IUI success among women within the same age group. Methods This retrospective cohort study comprised women who underwent IUI with donor sperm (IUI‐D) or husband sperm (IUI‐H) from 2017 to 2021. The women were stratified based on their age at the initiation of insemination into four categories: <35, 35–37, 38–39 and ≥40 years. Results A total of 5253 women undergoing 10 415 insemination cycles (3354 with IUI‐D and 7061 with IUI‐H) were included. The CLBRs decreased significantly with increasing maternal age within donor and husband insemination groups (P < 0.001). In the IUI‐D group, the crude CLBRs were 61.50% in women aged <35, 48.91% in 35–37, 24.14% in 38–39 and 11.76% in the ≥40‐year age category, respectively. The corresponding rates in the IUI‐H group were 27.62%, 22.96%, 13.73% and 6.90%, respectively. Within the <35 and 35–37‐year age categories, the CLBRs were significantly higher following IUI‐D cycles compared to IUI‐H cycles, with hazard ratios (HR) of 1.85 (1.68–2.04) and 1.69 (1.16–2.47), respectively. However, within the 38–39 and ≥40‐year age categories, both IUI‐D and IUI‐H resulted in comparable low CLBRs, with HRs of 1.91 (0.77–4.76) and 1.80 (0.33–9.86), respectively. Conclusion Advanced maternal age affects the whole process of fertility. Therefore, it could be reasonable to limit the number of IUI performed in women aged 40 years and older, even in couple using donor sperm for reproduction.

Competent blastocyst and receptivity endometrium improved clinical pregnancy in fresh embryo transfer cycles: a retrospective cohort study

Article

Full-text available

Apr 2024

Background Embryo quality is usually regarded as a key predictor of successful implantation and clinical pregnancy potential. The identification of embryos that have the capacity to implant and result in a healthy pregnancy is a crucial part of in vitro fertilization (IVF). Usually, morphologically high-quality embryos are chosen for embryo transfer in IVF treatment. The aim of this study was to assess the association between the available blastocyst formation rate and the clinical pregnancy outcome following the first fresh embryo transfer cycle and provide systematic individual treatment to adjust endometrial receptivity for the next transfer cycle. Methods This retrospective, single-center study included 512 fresh embryo transfers conducted between 11/2019 and 08/2021, which consisted of 385 cleavage-stage (Day 3) and 127 blastocyst-stage (Day 5) embryo transfers. The two groups were divided into a clinical pregnancy group and a nonclinical pregnancy group for comparison. The association between the available blastocyst formation rate and the clinical pregnancy rate in the Day 3 and Day 5 transfer groups were considered. Results In the Day 3 group, there were 275 clinical pregnancies, and the clinical pregnancy rate was 71.43%. Although the two pronuclei (2PN) oocyte rate and available embryo rate at Day 3 were significantly higher in the clinical pregnancy group than the nonclinical pregnancy group (P < 0.05), the blastocyst formation rate and the available blastocyst formation rate were not significantly different between the clinical pregnancy group and the nonclinical pregnancy group (P > 0.05). In the Day 5 group, there were 81 clinical pregnancies, and the clinical pregnancy rate was 63.78%. No baseline characteristics showed any obvious differences between the clinical pregnancy group and nonclinical pregnancy group (P > 0.05). The blastocyst formation rate in the nonclinical pregnancy group was higher than that in the clinical pregnancy group, but the difference was not statistically significant (81.06% vs. 77.03%, P = 0.083). Interestingly, the available blastocyst formation rate and the Day 5 available blastocyst formation rate were significantly higher in the nonclinical pregnancy group than the clinical pregnancy group (66.19% vs. 60.79%, P = 0.014; 54.58% vs. 46.98%, P = 0.007). Conclusions In fresh cycles, the available blastocyst formation rate was not associated with the clinical pregnancy outcome for Day 3 embryo transfers, and the available blastocyst formation rate was not positively correlated with the clinical pregnancy outcome for Day 5 embryo transfers.

Single Blastocyst-Stage Embryo Transfer should be Promoted for IVF Cycles Using Donor Sperm (IVFD)

Article

Full-text available

Mar 2024
CLIN EXP OBSTET GYN

Background Twin pregnancies carry significant fetal, perinatal and maternal risks. Thus, it is important to evaluate clinical outcomes of in vitro fertilization with donor sperm (IVFD) in the first attempt with double cleavage-stage embryos and explore optimal number of day 3 high-quality embryos for the blastocyst transfer on day 5. Methods We retrospectively identified all IVFD embryo transfers (IVFD-ETs) for the initial time between 2014 and 2021 at our hospital. We mainly analyzed the twin pregnancy rates for double day 3 embryo transfers and clinical outcomes of day 5 blastocyst transfers by prolonged culture with different numbers of day 3 high-quality embryos. Results Among 1512 IVFD-ETs, 834 were day 3 embryo transfers and 678 were day 5 blastocyst transfers. Our data indicated that the twin pregnancy rates reached up to 40% in the 674 double cleavage-stage embryo transfers and it was not due to the quality of the transferred embryos. For prolonged culture with 2, 3 and 4 day 3 high-quality embryos, the cycle rates of no high-quality blastocysts obtained were 30.43%, 19.80% and 7.91%, respectively. The clinical pregnancy rates were 56.52%, 74.26% and 72.32%, respectively. The twin pregnancies rates were 7.69%, 14.67% and 6.77%, respectively. Conclusions Transferring double cleavage-stage embryos had high risks of twin pregnancies in the IVFD-ETs. Blastocyst transfer was safe and recommended for the patients with three or more high-quality embryos on day 3.

Influence of maternal age on the birthweight of infants delivered from frozen-thawed blastocyst transfer cycles

Article

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Jul 2023

The aim of this study was to investigate whether maternal age had an effect on the birthweight of singletons delivered from frozen-thawed blastocyst transfer (FBT) cycles. A total of 1203 FBT cycles occurring between July 2011 and June 2021 at a single centre were retrospectively analysed. Based on the maternal age at FBT, the patients were divided into four groups: <30, 30–34, 35−37, and ≥38 years of age. Main outcomes measured included singleton birthweights, preterm births, large-for-gestational-age (LGA) and small-for-gestational-age (SGA) live births among the groups. There was no significant difference in birth weight among the four groups, while the highest birth weight was found in the <30 years group. The incidence of very preterm births and very low birth weights demonstrated an increasing trend with age; on the contrary, the incidence of preterm births, low birth weight (LBW), high birth weight and LGA and SGA live births gradually decreased with increasing age, but these differences were not statistically significant among groups (P>0.05, respectively). Although the proportion of females was lower than that of males, the difference was not statistically significant among the groups. After adjusting for possible confounders, maternal age was found to have no effect on adverse neonatal outcomes in the regression analyses (P>0.05). Birthweight in singleton births from FBT was not affected by maternal age.

Sperm banking

Chapter

Jan 2025

Differences in medically assisted reproduction use by sexual identity and partnership: a prospective cohort of cisgender women

Article

Apr 2024
HUM REPROD

STUDY QUESTION Does medically assisted reproduction (MAR) use among cisgender women differ among those with same-sex partners or lesbian/bisexual identities compared to peers with different-sex partners or heterosexual identities? SUMMARY ANSWER Women with same-sex partners or lesbian/bisexual identities are more likely to utilize any MAR but are no more likely to use ART (i.e. IVF, reciprocal IVF, embryo transfer, unspecified ART, ICSI, and gamete or zygote intrafallopian transfer) compared to non-ART MAR (i.e. IUI, ovulation induction, and intravaginal or intracervical insemination) than their different-sex partnered and completely heterosexual peers. WHAT IS KNOWN ALREADY Sexual minority women (SMW) form families in myriad ways, including through fostering, adoption, genetic, and/or biological routes. Emerging evidence suggests this population increasingly wants to form genetic and/or biological families, yet little is known about their family formation processes and conception needs. STUDY DESIGN, SIZE, DURATION The Growing Up Today Study is a US-based prospective cohort (n = 27 805). Participants were 9–17 years of age at enrollment (1996 and 2004). Biennial follow-up is ongoing, with data collected through 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS Cisgender women who met the following criteria were included in this sample: endorsed ever being pregnant; attempted a pregnancy in 2019 or 2021; and endorsed either a male- or female-sex partner OR responded to questions regarding their sexual identity during their conception window. The main outcome was any MAR use including ART (i.e. procedures involving micromanipulation of gametes) and non-ART MAR (i.e. nonmanipulation of gametes). Secondary outcomes included specific MAR procedures, time to conception, and trends across time. We assessed differences in any MAR use using weighted modified Poisson generalized estimating equations. MAIN RESULTS AND THE ROLE OF CHANCE Among 3519 participants, there were 6935 pregnancies/pregnancy attempts and 19.4% involved MAR. A total of 47 pregnancies or pregnancy attempts were among the same-sex partnered participants, while 91 were among bisexual participants and 37 among lesbian participants. Participants with same-sex, compared to different-sex partners were almost five times as likely to use MAR (risk ratio [95% CI]: 4.78 [4.06, 5.61]). Compared to completely heterosexual participants, there was greater MAR use among lesbian (4.00 [3.10, 5.16]) and bisexual (2.22 [1.60, 3.07]) participants compared to no MAR use; mostly heterosexual participants were also more likely to use ART (1.42 [1.11, 1.82]) compared to non-ART MAR. Among first pregnancies conceived using MAR, conception pathways differed by partnership and sexual identity groups; differences were largest for IUI, intravaginal insemination, and timed intercourse with ovulation induction. From 2002 to 2021, MAR use increased proportionally to total pregnancies/pregnancy attempts; ART use was increasingly common in later years among same-sex partnered and lesbian participants. LIMITATIONS, REASONS FOR CAUTION Our results are limited by the small number of SMW, the homogenous sample of mostly White, educated participants, the potential misclassification of MAR use when creating conception pathways unique to SMW, and the questionnaire’s skip logic, which excluded certain participants from receiving MAR questions. WIDER IMPLICATIONS OF THE FINDINGS Previous studies on SMW family formation have primarily focused on clinical outcomes from ART procedures and perinatal outcomes by conception method, and have been almost exclusively limited to European, clinical samples that relied on partnership data only. Despite the small sample of SMW within a nonrepresentative study, this is the first study to our knowledge to use a nonclinical sample of cisgender women from across the USA to elucidate family formation pathways by partnership as well as sexual identity, including pathways that may be unique to SMW. This was made possible by our innovative approach to MAR categorization within a large, prospective dataset that collected detailed sexual orientation data. Specifically, lesbian, bisexual, and same-sex partnered participants used both ART and non-ART MAR at similar frequencies compared to heterosexual and different-sex partnered participants. This may signal differential access to conception pathways owing to structural barriers, emerging conception trends as family formation among SMW has increased, and a need for conception support beyond specialized providers and fertility clinics. STUDY FUNDING/COMPETING INTEREST(S) The research reported in this publication was supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health (NIH), under award number R01MD015256. Additionally, KRSS is supported by NCI grant T32CA009001, AKH by the NCI T32CA057711, PC by the NHLBI T32HL098048, BM by the Stanford Maternal Child Health Research Institute Clinical Trainee Support Grant and the Diversity Fellowship from the American Society for Reproductive Medicine Research Institute, BGE by NICHD R01HD091405, and SM by the Thomas O. Pyle Fellowship through the Harvard Pilgrim Health Care Foundation and Harvard University, NHLBI T32HL098048, NIMH R01MH112384, and the William T. Grant Foundation grant number 187958. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The first author recently had a leadership role in the not-for-profit program, The Lesbian Health Fund, a research fund focused on improving the health and wellbeing of LGBTQ+ women and girls. The fund did not have any role in this study and the author’s relationship with the fund did not bias the findings of this manuscript. TRIAL REGISTRATION NUMBER N/A.

Paternal age does not jeopardize the live birth rate and perinatal outcomes after in vitro fertilization: an analysis based on 56,113 frozen embryo transfer cycles

Article

Nov 2023
AM J OBSTET GYNECOL

Sperm centriolar factors and genetic defects that can predict pregnancy

Article

Jul 2023
FERTIL STERIL

The human sperm centrosome, comprising the two morphologically distinct centrioles and associated pericentriolar materials, plays a crucial role in fertilization and early embryonic development after fertilization. Once inside the oocyte, the sperm centrosome serves as a microtubule organizing center, orchestrating mitotic spindle formation, chromosome segregation, and syngamy. Abnormalities of the sperm centrosome can lead to abnormal embryonic development, embryo chromosomal instability, and are associated with pregnancy loss. Recent research has shed light on the molecular composition, regulation, and function of this vital organelle. Understanding the intricacies of the sperm centrosome is crucial for elucidating the mechanisms underlying successful fertilization and early embryonic development, as well as addressing infertility and developmental disorders associated with centrosomal defects.

Kinderwunschtherapie mit Spendersamen – auf welcher Basis entscheiden wir über Umfang und Konsequenzen der vorausgehenden Diagnostik?Treatment of infertility with donor sperm—What is the basis for deciding on the extent and consequences of the preceding diagnostics?

Article

Mar 2023

High percentages of embryos with 21, 18 or 13 trisomy are related to advanced paternal age in donor egg cycles

Article

Full-text available

Jan 2018

Objective: Advanced paternal age is related to poor sperm quality; however, little is known on its effect on aneuploidy embryo rates and, more importantly, on chromosomal abnormalities like trisomy 21, 18 and 13. The objective of this study was to evaluate the effect of advanced paternal age on the trisomy rates of the chromosomes 21, 18 or 13 in embryos obtained from donated oocytes. Methods: A total of 378 embryos, obtained from 52 IVF/ICSI cycles with donated oocytes in conjunction with PGD, were allocated according to paternal age in three groups: Group A: ≤39 years (n=115 embryos), Group B: 40-49 years (n=157 embryos) and Group C: ≥50 year (n=106 embryos). Fertilization rates, embryo quality at day 3, blastocysts development, and aneuploidy embryo rates were then compared. Results: There was no difference in seminal parameters (volume, concentration and motility) in the studied groups. Fertilization rate, percentages of zygotes that underwent cleavage, and good-quality embryos on Day 3 were similar between the three groups evaluated. The group of men ≥50 years had significantly more sperm with damaged DNA, higher global aneuploidy rates, and significantly more embryos with trisomy 21, 18 or 13 compared to the other two evaluated groups (p<0.05). Conclusion: Our data shows that advanced paternal age increases global chromosomal abnormalities, and percentages of trisomy 21, 18 or 13 in embryos, and such effect is significantly important as of the age of 50. Embryo genetic screening is highly recommended in patients in which paternal age is ≥50 years old.

Do same sex couples and single women undergoing ovulation induction with oral agents and intrauterine insemination have outcomes comparable to infertile heterosexual couples?

Article

Full-text available

Sep 2017
FERTIL STERIL

National trends and outcomes of autologous in vitro fertilization cycles among women ages 40 years and older

Article

Full-text available

Jul 2017
J ASSIST REPROD GEN

Purpose: The purpose of the study was to describe trends in and investigate variables associated with clinical pregnancy and live birth in autologous in vitro fertilization (IVF) cycles among women ≥40 years. Methods: We used autologous IVF cycle data from the National ART Surveillance System (NASS) for women ≥40 years at cycle start. We assessed trends in fresh and frozen cycles (n = 371,536) from 1996 to 2013. We reported perinatal outcomes and determined variables associated with clinical pregnancy and live birth in fresh cycles between 2007 and 2013. Results: From 1996 to 2013, the total number of cycles in women ≥40 years increased from 8672 to 28,883 (p < 0.0001), with frozen cycles almost tripling in the last 8 years. Cycles in women ≥40 years accounted for 16.0% of all cycles in 1996 and 21.0% in 2013 (p < 0.0001). For fresh cycles from 2007 to 2013 (n = 157,890), the cancelation rate was 17.1%. Among cycles resulting in transfer (n = 112,414), the live birth rate was 16.1%. The following were associated with higher live birth rates: multiparity, fewer prior ART cycles, use of standard agonist or antagonist stimulation, lower gonadotropin dose, ovarian hyperstimulation syndrome, more oocytes retrieved, use of pre-implantation genetic screening/diagnosis, transferring more and/or blastocyst stage embryos, and cryopreserving more supernumerary embryos. Of the singleton infants born (n = 14,992), 86.9% were full term and 88.3% normal birth weight. Conclusions: The NASS allows for a comprehensive description of IVF cycles in women ≥40 years in the USA. Although live birth rate is less than 20%, identifying factors associated with IVF success can facilitate treatment option counseling.

Online sperm donation: A survey of the demographic characteristics, motivations, preferences and experiences of sperm donors on a connection website

Article

Full-text available

Jul 2016

Study question: What are the demographic characteristics, motivations, preferences and experiences of heterosexual, gay and bisexual sperm donors on a connection website (i.e. a website that facilitates direct contact between donors and recipients of gametes)? Summary answer: This demographically diverse group of men was donating for altruistic reasons and perceived the website as providing greater choice over donation arrangements: approximately one third favoured anonymous donation, most of whom were heterosexual, whilst gay and bisexual donors were more likely to be in contact with children conceived with their sperm. What is known already: Despite substantially more sperm donors being registered on connection websites than with clinics, there has been very little research on this population. Current understanding of the impact of sexual orientation on donors' attitudes is also limited. Study design, size, duration: An online survey was conducted over 7 weeks with 383 men registered as sperm donors with Pride Angel, a large UK-based connection website for donors and recipients of sperm. Participants/materials, setting, methods: The survey obtained data on participants' demographic characteristics and their motivations, preferences and experiences regarding online sperm donation, including attitudes towards contact with offspring. Differences according to participants' sexual orientation were examined. Main results and the role of chance: Most participants (80.4%, 308) were heterosexual, 10.5% (40) were gay and 9.1% (35) were bisexual; ages ranged from 18 to 69 years (median = 36, mean = 37.3, SD = 9.7). A greater proportion of gay and bisexual men desired open-identity donation (P < 0.005) and contact with offspring (P <0.005) than heterosexual men. Approximately one third (28.7%, 110) had donated sperm; 18.3% (70) had conceived at least one child, of whom a minority (25.7%, 18) were currently in contact with the child, comprising significantly more gay and bisexual than heterosexual men (P = 0.001). Heterosexual men were most likely to state a preference for natural insemination, although the large majority (94.3%, 66) of donors who had conceived children had used artificial insemination. Limitations, reasons for caution: Findings may not be representative of all sperm donors using connection websites because members of only one website participated and participants were, by necessity, a self-selected sample. Wider implications of the findings: This is the first comprehensive study of donors who connect with recipients via the internet, including a substantial number who have donated and conceived children. The findings indicate that sexual orientation may influence men's donation preferences and raise policy issues concerning donor recruitment and the incorporation of online sperm donation into clinical practice. Study funding/competing interests: This study was supported by the Wellcome Trust (097857/Z/11/Z). E.T. is the co-founder of Pride Angel; the remaining authors have no conflicts of interest.

Sexual orientation of women does not affect outcome of fertility treatment with donated sperm

Article

Full-text available

Jan 2014
HUM REPROD

Is there a difference in fertility between heterosexual women and lesbians undergoing sperm donation? Women undergoing treatment with donated sperm are equally fertile regardless of sexual orientation. Lesbians have an increased prevalence of smoking, obesity, sexually transmitted diseases and, possibly, polycystic ovary syndrome, all factors known to affect fertility. Previous studies on sperm donation inseminations (D-IUI) show conflicting results regarding pregnancy outcome. This is a national study of 171 lesbians and 124 heterosexual women undergoing sperm donation both as D-IUI (lesbian n = 438, heterosexual n = 298) and as embryo transfers (ET) after IVF with donated sperm (lesbians n = 225, heterosexuals n = 230) during 2005-2010. All clinics in Sweden offering sperm donation recruited patients. Differences in patients' medical history, treatment results and number of treatments to live birth were analyzed using independent samples t-test, Pearson's χ(2) test or Fisher's exact probability test. 71.8% of heterosexuals and 69.0% of lesbians had a child after treatment. The mean number of treatments was 4.2 for heterosexual women and 3.9 for lesbians. The total live birth rate, regardless of treatment type, was 19.7% for heterosexuals and 19.5% for lesbians. For D-IUI, the live birth rate was 12.8% for heterosexuals and 16.0% for lesbians and the live birth rate for all IVF embryo transfers (fresh and thawed cycles) was 28.7% for heterosexuals and 26.2% for lesbians. There were no differences in live birth rate between the groups for each of the different types of insemination stimulations (natural cycle; clomiphene citrate; FSH; clomiphene citrate and FSH combined). Nor was there a difference in live birth rate between the groups for either fresh or thawed embryo transfer. There was no difference between the proportions of women in either group or the number of treatments needed to achieve a live birth. Heterosexuals had a higher prevalence of smokers (9.2%), uterine polyps (7.2%) or previous children (11.3%) than lesbians (smokers 2.8%, P = 0.03; polyps 1.8%, P = 0.03; child 2.5%, P = 0.003). This study is limited to women living in stable relationships undergoing treatment with donated sperm in a clinical setting and may not apply to single women or those undergoing home inseminations. These results may influence healthcare policy decisions as well as increase the quality of clinical care and medical knowledge of healthcare professionals. The data also have important implications for individuals regarding screening, infertility diagnostic procedures and treatment types offered to heterosexuals and lesbians seeking pregnancy through sperm donation. Funding was granted by the Stiftelsen Familjeplaneringsfonden i Uppsala; the Swedish Research Council for Health, Working Life and Welfare; and the Marianne and Marcus Wallenberg Foundation. The authors report no conflicts of interest.

Advanced paternal age and the risk of spontaneous abortion: an analysis of the combined 2011-2013 and 2013-2015 National Survey of Family Growth

Article

May 2019
AM J OBSTET GYNECOL

Background: Maternal and paternal age at first birth are increasing across the global population. Spontaneous abortion, one of the most common abnormal pregnancy outcomes, is known to occur more frequently with increasing maternal age. However, the relationship of advanced paternal age and spontaneous abortion is poorly understood, and previous results have yielded conflicting results. Objective: To examine the influence of paternal age on the risk of spontaneous abortion among singleton pregnancies conceived without assisted reproductive technologies. Materials and methods: This was a retrospective, case-control study using combined pregnancy data from the Centers for Disease Control and Prevention's 2011-2013 and 2013-2015 National Survey of Family Growth. Spontaneous, singleton pregnancy data from women aged 15-45 years were analyzed. Ongoing pregnancies, induced abortions, ectopic pregnancies, preterm births, and intrauterine fetal deaths were excluded. Bivariate associations of pregnancy outcome (spontaneous abortion at <20 weeks and ≤12 weeks vs. live birth at ≥37 weeks) and paternal age were determined, along with those of maternal age and selected demographic and pregnancy characteristics. Significant associations were included in a multivariable logistic regression, which accounted for multiple pregnancies derived from the same respondent. Results: A total of 12,710 pregnancies from 6979 women were analyzed, consisting of 2300 (18.2%) spontaneous abortions and 10,410 (81.8%) term live births. Median maternal and paternal ages were 25 and 28 years, respectively. After adjusting for maternal age, race/ethnicity, socioeconomic status, marital status, and pregnancy intention, pregnancies resulting in spontaneous abortions had 2.05 (95% confidence interval, 1.06-2.20) times the odds of being from a father aged 50 years or older, vs. 25-29 years of age. These relationships remained significant when defining SABs at ≤12 weeks (adjusted odds ratio, 2.30; 95% confidence interval, 1.17-4.52). Conclusion: Paternal age may increase the odds of spontaneous abortion, independent of selected factors, including demographics, pregnancy intention, and maternal age. This association was robust across several gestational age-based definitions of spontaneous abortion, even after adjustment.

Births in the United States, 2017

Article

Aug 2018

This report presents selected highlights from 2017 final birth data on key demographic, health care utilization, and infant health indicators. General fertility rates (the number of births per 1,000 females aged 15-44 years) and teen birth rates are presented by race and Hispanic origin. The use of Medicaid as the source of payment for the delivery and preterm birth rates are presented by the age of the mother. Data for 2017 are compared with 2016 for each indicator. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.

Births in the United States, 2014

Article

Sep 2015

For the first year since 2007, childbearing rose in the United States in 2014, albeit slightly. Trends differed by race and Hispanic origin, with the GFR up among non-Hispanic white and API women but down or unchanged among other groups for 2013–2014. Historical lows in teen childbearing were seen in the U.S. overall in 2014, and for each of the race and Hispanic origin groups. Following years of steady increases that totaled nearly 60% (3), the U.S. cesarean delivery rate declined for the second straight year. Cesarean delivery rates had been on the decline for several years for non-Hispanic white and API women, but 2014 marks the first year of decline in cesarean deliveries among non-Hispanic black and Hispanic women. Preterm birth rates continued to trend downward in 2014 (2), overall and among most race and Hispanic origin groups, but large differences among groups in the risk of preterm birth were observed. The forthcoming report, "Births: Final data for 2014" (4), will present more information on the topics addressed in this report and selected others. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.

Comparison of perinatal outcomes following fresh and frozen-thawed blastocyst transfer

Article

Jun 2016
INT J GYNECOL OBSTET

Objective: To investigate the effect of ovarian stimulation on endometrial receptivity by comparing singleton pregnancy and perinatal outcomes following fresh or frozen-thawed blastocyst transfers. Methods: A retrospective cohort study enrolled patients undergoing fresh or frozen-thawed blastocyst transfers that resulted in live deliveries between January 1, 2010 and September 30, 2013 at a single academic center. Implantation, clinical pregnancy, spontaneous abortion, and live delivery rates were calculated. The incidence of term delivery, preterm delivery, low birth weight, term low birth weight, and very low birth weight were also recorded. To detect a 10% difference in the implantation rate, a minimum sample size of at least 415 transfer cycles in each group was estimated. Results: The study included data from 918 fresh and 1273 frozen-thawed cycles. Patients in both groups were of similar age and there was no difference in the grading of blastocysts. No differences were observed in the implantation (37.3% vs 37.7%), clinical pregnancy (50.2% vs 49.4%), spontaneous abortion (7.3% vs 9.3%), and live delivery (42.9% vs 40.6%) rates of the two groups. A sub-analysis of all live singleton and twin deliveries revealed no difference in perinatal outcomes between the two techniques. Conclusions: The present study demonstrated equivalent singleton pregnancy and perinatal outcomes when comparing frozen-thawed and fresh blastocyst transfer procedures.

Impact of elevated peak serum estradiol levels during controlled ovarian hyperstimulation on the birth weight of term singletons from fresh IVF-ET cycles

Article

Feb 2015
J ASSIST REPROD GEN

To investigate the impact of elevated serum estradiol (E2) levels on the day of hCG trigger on the birth weight of term singletons after fresh In Vitro Fertilization (IVF)-Embryo Transfer (ET) cycles. Retrospective cohort study of all patients initiating fresh IVF-ET cycles resulting in live births between January 2004 and February 2013. The incidence of low birthweight (LBW) term singletons in patients with E2 levels on day of hCG trigger above or below the 95 % cutoff for E2 values in our clinic (3,069.2 pg/mL) was estimated. Multiple gestations and vanishing twin pregnancies were excluded. Two thousand nine hundred thirty-nine singleton live births were identified for inclusion. One hundred forty seven (5 %) and 2792 (95 %) live singleton births occurred in patients with peak E2 levels above and below 3,069.2 pg/mL, respectively. The overall incidence of term LBW was 5.4 % in the >3,069.2 pg/mL group compared to 2.4 % in the ≤3,069.2 pg/mL group (P = .038). An E2 level >3,069.2 pg/mL on the day of hCG administration was associated with increased odds of LBW term singletons (OR = 2.29; 95 % CI = 1.03-5.11). The increased odds remained unchanged when adjusting for maternal age (aOR = 2.29; 95 % CI = 1.02-5.14; P = .037), gestational age at delivery (aOR = 2.04; 95 % CI = 1.22-3.98; P = .025), and day 3 versus blastocyst transfer (aOR = 2.5; 95 % CI = 1.11-5.64; P = .023). Peak E2 level >3,069.2 pg/mL is associated with increased odds of LBW term singletons after fresh IVF-ET cycles. Conservative stimulation protocols aiming not to exceed an E2 level of 3,000 pg/mL may be advantageous for placentation and fetal growth if a fresh transfer is planned.

Reproductive outcomes of women aged 40 and older undergoing IVF with donor sperm

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