scholarly journals Live Birth Rate in Patients With Premature Ovarian Insufficiency During Long-Term Follow-Up Under Hormone Replacement With or Without Ovarian Stimulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Bunpei Ishizuka ◽  
Masataka Furuya ◽  
Machiko Kimura ◽  
Eri Kamioka ◽  
Kazuhiro Kawamura
Keyword(s):  
Ovarian Stimulation ◽  
Chromosomal Abnormalities ◽  
Intrauterine Insemination ◽  
Hormone Replacement ◽  
Age Groups ◽  
Live Birth Rate ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency

We analyzed data from 466 patients with premature ovarian insufficiency (POI) who wished to have a biological child and were followed up while undergoing hormone replacement (HR) therapy with or without ovarian stimulation (OS) between April 2014 and December 2020. OS was conducted in 6891 cycles in 429 patients (Group OS), whereas only HR (Group HR) was conducted in 1117 cycles in 37 patients. The follicle growth rate was 48.3% (207/429) per patient in Group OS and 5.4% (2/37) in Group HR (p<0.01). There were 51 live births (LBs) in 50 patients during follow-up. In Group OS, the LB rate was 5.8% (47/807) in cycles where in vitro fertilization (IVF) and embryo transfer were attempted (Group IVF), and 1.3% (3/236) in cycles where intrauterine insemination/timed intercourse was attempted (p<0.01). No pregnancies occurred in Group HR. Among the patients in Group IVF, the LB rate was significantly higher in patients aged <35 years at the initiation of follow-up than in patients who started at later ages (p<0.01). Among the cases who achieved an LB, 39 were patients with idiopathic POI (Group IVF-1, n=297) and seven were patients who had undergone surgical treatment for benign ovarian tumors (Group IVF-2, n=50); however, no LBs occurred in patients who had undergone treatment for malignancy (n=17), and only one in patients with chromosomal abnormalities (n=22). The LB rate per case in the patients in Group IVF-1 and those aged <35 years at the start of follow-up (Group IVF-1-a) was 24.1% (26/108), which was higher than those of the other age groups. The LB rate per case in the patients in Group IVF-1-a with <4 years of amenorrhea was 37.3% (19/51), and that in the patients in Group IVF-2 with <4 years of amenorrhea was 21.2% (7/33). These results suggest that infertility treatment is possible in some patients with POI, especially those that can be classified in Group IVF-1-a and Group IVF-2 with <4 years of amenorrhea. Therefore, OS combined with HR therapy should be considered for such patients before attempts at oocyte donation.

scholarly journals Discovery and Preclinical Development of Orally Active Small Molecules that Exhibit Highly Selective Follicle Stimulating Hormone Receptor Agonism

2021 ◽  
Vol 11 ◽  
Author(s):  
Selva Nataraja ◽  
Henry Yu ◽  
Joie Guner ◽  
Stephen Palmer
Keyword(s):  
Ovarian Stimulation ◽  
Hormone Receptor ◽  
Ovulation Induction ◽  
Low Dose ◽  
Intrauterine Insemination ◽  
Follicle Stimulating Hormone ◽  
Controlled Ovarian Stimulation ◽  
Orally Active ◽  
Stimulating Hormone

An orally active follicle stimulating hormone receptor allosteric agonist would provide a preferred treatment for over 16 million infertile women of reproductive age in low complexity methods (ovulation induction-intrauterine insemination) or in high complexity methods (controlled ovarian stimulation-in vitro fertilization). We present two oral follicle stimulating hormone receptor allosteric agonist compounds that have the desired pharmacology, drug metabolism, pharmacokinetics, and safety profile for clinical use. These molecules provide a single agent suitable for ovulation induction-intrauterine insemination or controlled ovarian stimulation-in vitro fertilization that is more convenient for patients and achieves similar preclinical efficacy as rec-hFSH. TOP5668, TOP5300 were evaluated in vitro in Chinese hamster ovary cells transfected with individual glycoprotein receptors measuring cAMP (FSHR, LH/CGR, thyroid stimulating hormone receptor). TOP5668 was found to have solely follicle stimulating hormone receptor allosteric agonist activity while TOP5300 was found to have mixed follicle stimulating hormone receptor allosteric agonist and LHR-AA activity. Both compounds stimulated concentration-dependent increases in estradiol production from cultured rat granulosa cells in the presence or absence of low dose rec-hFSH, while only TOP5300 stimulated testosterone production from rat primary Leydig cells. In pooled human granulosa cells obtained from patients undergoing controlled ovarian stimulation-in vitro fertilization, TOP5300 stimulated 7-fold greater maximal estradiol response than rec-hFSH and TOP5668 was 10-fold more potent than TOP5300. Both TOP5300 and TOP5668 stimulated follicular development in immature rat to the same efficacy as recombinant follicle stimulating hormone. In mice treated with TOP5300, in the presence of low dose of follicle stimulating hormone, there were no differences in oocyte number, fertilization rate, and hatched blastocyst rate in mice with TOP5300 and low dose follicle stimulating hormone vs. reference proteins pregnant mare serum gonadotropin or high dose rec-hFSH. ADME/PK and safety profiles were favorable. In addition, there was no appreciable activity on thyroid hormones by TOP5300 in 14-days toxicological study in rat or dog. The selected lead compound, TOP5300 stimulated a more robust increase in estradiol production from granulosa-lutein cells from women with polycystic ovarian syndrome patient compared to rec-hFSH. Conclusions: Two novel oral FSHR allosteric agonist, TOP5668 and TOP5300, were found to mimic the biological activity of rec hFSH in preclinical studies. Both compounds led to folliculogenesis and superovulation in rat and mice. Specifically, TOP5300 led to a similar number of ovulated oocytes that fertilized and developed into hatched blastocysts in mice when compared to rec-hFSH. The safety profile demonstrated lack of toxicity.

REPRODUCTIVE POTENTIAL OF WOMEN WITH PREMATURE OVARIAN INSUFFICIENCY

2021 ◽  
pp. 41-48
Author(s):  
Spiridenko G.Yu. ◽  
Petrov Yu.A. ◽  
Palieva N.V.
Keyword(s):  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Assisted Reproductive Technologies ◽  
Hormone Replacement ◽  
Reproductive Potential ◽  
Reproductive Technologies ◽  
Pathological Process ◽  
Reproductive Age ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency

Infertility is currently a priority problem for women of reproductive age. One of the reasons for this condition may be premature ovarian insufficiency. This is a pathological process causes by primary hypogonadism that occurs in women under 40 years of age. Its prevalence varies from 1:10,000 at the age of 20 to 1:100 at an older age. The absence of specific clinical manifestations of the disease complicates its early diagnosis and timely treatment. This pathological process manifests itself as secondary oligo-or amenorrhea, infertility. Less often, before the onset of reproductive disorders, there are manifestations of estrogenic insufficiency - vasomotor disorders - hot flashes, hyperhidrosis, cephalgia, tachycardia, arterial hypertension, emotional and vegetative disorders-irritability, asthenic manifestations, anxiety, depression, hypo - thymia, decreased libido. The lack of accurate data on etiological factors makes it harder to find methods for preventing this disease. The main direction of treatment is hormone replacement therapy, aimed at eliminating the insufficiency of natural estrogens in the woman's body. The chances of successful realization of the reproductive potential depend on the value of the follicle-stimulating hormone, since its high concentration affects the mitotic activity of granulosa cells of the follicle, which confirms the validity of hormone replacement therapy. The non-occurrence of pregnancy after therapy forces the patient to use assisted reproductive technologies using donor embryos and oocytes, while the effectiveness of in vitro fertilization does not exceed 58%. To prevent this outcome, if a woman has risk factors for developing premature ovarian insufficiency, it is necessary to timely assess the ovarian reserve with the preservation of her own oocytes for subsequent assisted reproductive technologies.

scholarly journals Comparative study of assisted reproductive outcomes between young patients with occult premature ovarian insufficiency and advanced-age patients

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052093465
Author(s):  
Ling-nv Yao ◽  
Wen-qin Lin ◽  
Nan Jiang ◽  
Chuyan Li ◽  
Hai-feng Cao ◽  
...  
Keyword(s):  
Live Birth ◽  
Ovarian Reserve ◽  
Embryo Implantation ◽  
Young Patients ◽  
Abortion Rate ◽  
Advanced Age ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Vitro Fertilization

Objective The purpose of this study was to compare the pregnancy outcomes among young patients with occult premature ovarian insufficiency (OPOI), advanced-age patients with diminished ovarian reserve (DOR), and advanced-age patients with normal ovarian reserve. Methods We retrospectively reviewed 324 women who underwent their first cycles of in vitro fertilization/intracytoplasmic sperm injection. The women were divided into the following groups: young women with OPOI, advanced-age women with DOR, and advanced-age women with normal ovarian reserve. The outcomes were compared among the different groups: Results The rates of live birth and embryo implantation in the young OPOI group were significantly higher than in the advanced-age DOR group, but comparable to those in the advanced-age normal ovarian reserve group. Moreover, the abortion rate was significantly lower in young OPOI patients compared with advanced-age patients with or without DOR. Conclusion Higher embryo implantation and live birth rates and a lower abortion rate can be achieved in young patients with OPOI compared with older patients. The better outcomes in advanced-age patients with normal ovarian reserve compared with DOR may be related to egg quantity rather than quality.

scholarly journals Fertility Preservation Success Subsequent to Concurrent Aromatase Inhibitor Treatment and Ovarian Stimulation in Women With Breast Cancer

2015 ◽  
Vol 33 (22) ◽  
pp. 2424-2429 ◽  
Author(s):  
Kutluk Oktay ◽  
Volkan Turan ◽  
Giuliano Bedoschi ◽  
Fernanda S. Pacheco ◽  
Fred Moy
Keyword(s):  
Breast Cancer ◽  
In Vitro Fertilization ◽  
Fertility Preservation ◽  
Embryo Transfer ◽  
Ovarian Stimulation ◽  
Live Birth Rate ◽  
Embryo Cryopreservation ◽  
Vitro Fertilization ◽  
Embryo Freezing

Purpose We have previously reported an approach to ovarian stimulation for the purpose of fertility preservation (FP) in women with breast cancer via embryo freezing with the concurrent use of letrozole. The aim of this study was to provide the pregnancy and FP outcomes when embryos generated with the same protocol are used. Patients and Methods In all, 131 women with stage ≤ 3 breast cancer underwent ovarian stimulation and received concurrent letrozole 5 mg per day before receiving adjuvant chemotherapy and cryopreserving embryos. Results Thirty-three of the 131 women underwent 40 attempts to transfer embryos to their own uterus (n = 18) or via the use of a gestational carrier (n = 22) at a mean age of 41.5 ± 4.3 years with a median 5.25 years after embryo cryopreservation. The overall live birth rate per embryo transfer was similar to the US national mean among infertile women of a similar age undergoing in vitro fertilization–embryo transfer (45.0 v 38.2; P = .2). Seven (38.8%) of the 18 pregnancies were twins with no higher-order pregnancies being encountered. No fetal anomalies or malformations were reported in 25 children after a mean follow-up of 40.4 ± 26.4 months. Seventeen of the 33 women attempting pregnancy had at least one child, translating into an FP rate of 51.5% per attempting woman. Conclusion Embryo cryopreservation after ovarian stimulation with the letrozole and follicle-stimulating hormone protocol preserves fertility in women with breast cancer and results in pregnancy rates comparable to those expected in a noncancer population undergoing in vitro fertilization.

scholarly journals Analysis of in vitro follicle development during the onset of premature ovarian insufficiency in a mouse model

2017 ◽  
Vol 29 (8) ◽  
pp. 1538 ◽  
Author(s):  
Heidy Kaune ◽  
Sairah Sheikh ◽  
Suzannah A. Williams
Keyword(s):  
Mouse Model ◽  
Premature Ovarian Insufficiency ◽  
Controlled Environment ◽  
Follicle Development ◽  
Growth Morphology ◽  
Follicle Growth ◽  
Ovarian Insufficiency ◽  
Female Mice ◽  
And Control

Premature ovarian insufficiency (POI) occurs in 1% of women under 40 years of age and is predominantly idiopathic. In a transgenic mouse model of follicular POI, the Double Mutant (DM), female mice are fertile at 6 weeks of age, become infertile by 9 weeks and exhibit POI by 3 months. DM female mice generate oocytes lacking mucin O-glycans and complex N-glycans due to deletion of core 1 synthase, glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1 (C1galt1) and mannoside acetylglucosaminyltransferase 1 (Mgat1) respectively (DM, C1galt1F/FMgat1F/F:ZP3Cre; Control, C1galt1F/FMgat1F/F). To determine whether DM follicle development could be improved in a controlled environment, follicles from DM and Control mice were cultured individually and follicle growth, morphology, survival and antrum formation were evaluated. DM ovaries were more rigid than Control ovaries at 3, 6 and 9 weeks, which was exacerbated with age, resulting in a failure to isolate follicles from 9 week-old DM females. DM follicles had decreased survival compared with Control follicles from females at 3 and 6 weeks of age. Furthermore, survival rate of DM follicles decreased with age between 3 and 6 weeks. DM follicles at both 3 and 6 weeks had accelerated follicle growth and altered antrum formation during the first few days of culture but, after 6 days, follicles were equivalent in size to the Controls. In conclusion, a population of DM follicles retain the potential to develop in vitro, and therefore follicle culture offers a reliable method to generate antral follicles from preantral follicles after the onset of POI in these female mice.

scholarly journals Analysis of parental abnormal chromosomal karyotype and subsequent live births in Chinese couples with recurrent pregnancy loss

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shan Li ◽  
Mei Chen ◽  
Peng-Sheng Zheng
Keyword(s):  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Chromosomal Abnormalities ◽  
Intrauterine Insemination ◽  
Genetic Diagnosis ◽  
Live Birth Rate ◽  
Tertiary Referral Hospital ◽  
Natural Conception ◽  
Balanced Translocations ◽  
The Impact

AbstractThe frequency and distribution of chromosomal abnormalities and the impact of parental chromosomal aberration on the pregnancy outcomes of couples with recurrent pregnancy loss remains controversial. 3235 RPL couples who experienced two or more miscarriages before 20 weeks were diagnosed in our tertiary referral hospital during 2008–2018 and included in the single-center retrospective cohort study covering a 10-year period. Chromosome aberration was detected in 121 (3.74%) among 3235 RPL couples which included 75 female and 46 male cases at an individual level. 101 cases were structural aberrations including balanced translocations in 46(38.0%) cases, Robertsonian translocations in 13(10.7%) cases, inversions in 42(34.7%) cases and 20(16.5%) cases were numerical aberrations. 121 carriers and 428 non-carriers were followed up for two years, 55 carriers and 229 non-carriers were subsequent pregnant after diagnosis by natural conception or intrauterine insemination. The frequency of carriers to have a health newborn was not significantly different with non-carriers (72.7% vs. 71.2%, adjusted P = 0.968). This study described the majority of carriers were balanced translocations and chromosome aberrations had a limited influence on live birth rate from the present data. The results of the study also remind us that natural conception may be also a good alternative rather than PGD (Pre-implantation Genetic Diagnosis) which is common in many other reproductive centers for such patients.

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