Pregnancy after treatment with three recombinant gonadotropins

Agrawal, Rina; West, Christopher C.; Conway, GS; Page, Memia L; Hs, Jacobs

doi:10.1016/s0140-6736(05)62162-9

Cited by 42 publications

(8 citation statements)

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“…Agrawal et al 16 reported the first pregnancy after the use of recombinant follicle‐stimulating hormone, luteinising hormone and hCG in a patient with hypogonadotrophic hypogonadism following initial unsuccessful attempts using GnRH. Yet the case they reported did not ovulate in her first treatment cycle, over‐responded to the same doses of ovulation induction agents in her second cycle and developed severe ovarian hyperstimulation syndrome in her third cycle in which she eventually conceived.…”

Section: Discussionmentioning

confidence: 99%

“…We are aware that the best dose, duration or type of luteal phase support in infertility treatment is controversial, 14 and that the importance of luteal support in women with hypogonadotrophic hypogonadism was previously questioned in a study of two patients receiving hMG and hCG for ovulation induction proposing that 75 IU of luteinising hormone applied during the stimulation phase is sufficient to establish a normal follicular phase, normal luteal phase and even pregnancy. 15 Agrawal et al 16 reported the first pregnancy after the use of recombinant follicle-stimulating hormone, luteinising hormone and hCG in a patient with hypogonadotrophic hypogonadism following initial unsuccessful attempts using GnRH. Yet the case they reported did not ovulate in her first treatment cycle, over-responded to the same doses of ovulation induction agents in her second cycle and developed severe ovarian hyperstimulation syndrome in her third cycle in which she eventually conceived.…”

Section: Discussionmentioning

confidence: 99%

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Pregnancy following monofollicular ovulation induction with recombinant FSH, recombinant LH and timed coitus in an amenorrheic woman with long‐standing hypogonadotrophic hypogonadism

El-Shawarby

Turner

Reddy

et al. 2004

BJOG

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A 31 year old patient with primary amenorrhea, primary infertility and long-standing hypogonadotrophic hypogonadism presented to our infertility unit in June 2003. Immediately prior to her referral to our clinic, the patient was on sequential hormone replacement therapy for one year in view of moderate lumbar spine osteopenia detected on DEXA bone densitometry, which she discontinued because she wished to conceive. In the past, the patient used oral contraceptive pills to induce regular withdrawal bleeding.A routine series of infertility investigations was performed. Hormonal profile revealed follicle-stimulating hormone of 0.9 IU/L, luteinising hormone of 0.5 IU/L, hypoestrogenaemia, normal prolactin level, testosterone and DHEA-sulphate at the upper range of normal. Hysterosalpingography showed normal bilateral spillage of dye through the tubes, and a small uterine filling defect. Hysteroscopy was therefore arranged and a small benign uterine polyp was removed. Pelvic ultrasound scan revealed small inactive ovaries. Semen analysis of the male partner was normal.Management options of GnRH pump or gonadotrophin injections were discussed with the patient. She opted for gonadotrophin injections and was therefore commenced on recombinant follicle-stimulating hormone 50 IU (Follitropin beta, Puregon, Organon, The Netherlands) and recombinant luteinising hormone 75 IU (Lutropin alpha, Luveris, Serono, Switzerland) on day two of a withdrawal bleed, induced by a course of oral contraceptive pills. Serial transvaginal ultrasound measurements of follicular growth and endometrial thickness, together with hormonal determination of the levels of estradiol (E 2 ) and luteinising hormone, were used for monitoring of her cycle. The dose of recombinant follicle-stimulating hormone was increased to 75 IU on day 12 of the treatment cycle as there was no obvious follicular growth. Follow up was continued until on day 26 of treatment, when ultrasound scan showed a dominant follicle of 23 mm in diameter, endometrial thickness of 9.1 mm, E 2 level of 3155 pmol/L and luteinising hormone level of 3.3 IU/L. Human chorionic gonadotrophin (hCG, 5000 units; Profasi, Serono, Switzerland) was then administered and sexual intercourse was advised. A week later, a serum progesterone of 127 nmol/L confirmed ovulation. The patient became pregnant in this cycle. Unfortunately, the patient miscarried after the six week ultrasound scan and was managed by surgical evacuation of the uterus.Two months later, the patient was very keen to start another treatment cycle. A similar treatment protocol was followed in the second cycle except that the starting dose of recombinant follicle-stimulating hormone was increased to 75 IU. This time, she developed a dominant follicle of 24 mm on day 19 of treatment, endometrial thickness of 10.1 mm, E 2 and luteinising hormone level of 2231 pmol/L and 2.4 IU/L, respectively. Serum progesterone was also suggestive of ovulation at 64 nmol/L. Luteal phase support in the form of progesterone suppositories 400 mg daily (Cy...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pregnancy following monofollicular ovulation induction with recombinant FSH, recombinant LH and timed coitus in an amenorrheic woman with long‐standing hypogonadotrophic hypogonadism

El-Shawarby

Turner

Reddy

et al. 2004

BJOG

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“…Due to the rarity of this condition (~1% of infertile patients), most of the initial studies described some isolated case reports on the administration of both rFSH and rLH to treat HH patients. 10 , 57 – 62 …”

Section: Stimulation Of Follicular Development With Rfsh and Rlh In Wmentioning

confidence: 99%

“… 3 , 5 , 7 , 9 In recent years, the availability of both recombinant FSH (rFSH) and recombinant LH (rLH) has provided a new therapeutic option for HH patients. In 1997, Agrawal et al 10 reported the first birth in a hypopituitary–hypogonadotropic woman (World Health Organization [WHO] type I) following stimulation of follicular growth with rFSH and rLH.…”

Section: Introductionmentioning

confidence: 99%

Profile of follitropin alpha/lutropin alpha combination for the stimulation of follicular development in women with severe luteinizing hormone and follicle-stimulating hormone deficiency

Rinaldi¹,

Selman²

2016

IJWH

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A severe gonadotropin deficiency together with chronic estradiol deficiency leading to amenorrhea characterizes patients suffering from hypogonadotropic hypogonadism. Administration of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to these patients has been shown to be essential in achieving successful stimulation of follicular development, ovulation, and rescue of fertility. In recent years, the availability of both recombinant FSH (rFSH) and recombinant LH (rLH) has provided a new therapeutic option for the stimulation of follicular growth in hypopituitary–hypogonadotropic women (World Health Organization Group I). In this article, we review the data reported in the literature to highlight the role and the efficacy of using recombinant gonadotropins, rFSH and rLH, in the treatment of women with severe LH/FSH deficiency. Although the studies on this issue are limited and the experiences available in the literature are few due to the small number of such patients, it is clearly evident that the recombinant gonadotropins rFSH and rLH are efficient in treating patients affected by hypogonadotropic hypogonadism. The results observed in the studies reported in this review suggest that recombinant gonadotropins are able to induce proper follicular growth, oocyte maturation, and eventually pregnancy in this group of women. Moreover, the clinical use of recombinant gonadotropins in this type of patients has given more insight into some endocrinological aspects of ovarian function that have not yet been fully understood.

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“…During the early 1990s, several IVF programmes reported pregnancies following the use of recombinant FSH to induce ovulation for IVF [68][69][70]. In 1997, Agrawal et al [71] reported the first birth following stimulation of follicular growth in a hypopituitary-hypogonadotrophic woman (WHO Group I) with recombinant FSH and recombinant LH; recombinant hCG was used to induce ovulation. In 2002, Donderwinkel et al [72] reported a pregnancy following ovulation induction with rFSH in a patient with polycystic ovaries.…”

Section: Recombinant Gonadotropinsmentioning

confidence: 99%

Gonadotropin stimulation: past, present and future

Lunenfeld

2011

Reprod Medicine & Biology

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Gonadotropin therapy is so central to infertility treatment that it is easy to overlook the considerable discovery and research that preceded production of the effective and safe products available today. The history underpinning this development spans over 300 years and provides a splendid example of how basic animal experimentation and technological advances have progressed to clinical application. Following the discovery of germ cells in 1677 and realizing, in 1870, that fertilization involved the merging of two cell nuclei, one from the egg and one from sperm, it took another 40 years to discover the interplay between hypothalamus, pituitary and gonads. The potential roles of gonadotropin regulation were discovered in 1927. Gonadotropin, such as pregnant mare serum gonadotropin (PMSG), was first introduced for ovarian stimulation in 1930. However, use of PMSG leads to antibody formation, and had to be withdrawn. Following withdrawal of PMSG, human pituitary gonadotropin (HPG) and urinary menopausal gonadotropin (hMG) appeared on the market, and 50 years ago the first child was delivered by our group in 1961 and opened the path to controlled ovarian stimulation. HPG produced good results, but its use came to an end in the late 1980s when it was linked to the development of Creutzfeldt-Jakob disease (CJD). HMG preparations containing a high percentage of unknown urinary proteins, making quality control almost impossible, were then the only gonadotropins remaining on the market. With the availability of hMG, clomiphene citrate, ergot derivatives, GnRH agonists and antagonists, as well as metformin, algorithms were developed for their optimal utilization and were used for the next four decades. Following the first human IVF baby in 1978 and ICSI in 1991, such procedures became standard practice. The main agents for controlled ovarian stimulation for IVF were gonadotropins and GnRH analogues, with batch to batch consistent gonadotropic preparations; methods could be developed to predict and select the correct dose and the optimal protocol for each patient. We are now seeing the appearance of gonadotropin with sustained action and orally active GnRH analogues as well as orally active molecules capable to stimulate follicle growth and inducing ovulation. These new developments may one day remove the need for the classical gonadotropin in clinical work.

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Pregnancy after treatment with three recombinant gonadotropins

Cited by 42 publications

References 5 publications

Pregnancy following monofollicular ovulation induction with recombinant FSH, recombinant LH and timed coitus in an amenorrheic woman with long‐standing hypogonadotrophic hypogonadism

Pregnancy following monofollicular ovulation induction with recombinant FSH, recombinant LH and timed coitus in an amenorrheic woman with long‐standing hypogonadotrophic hypogonadism

Profile of follitropin alpha/lutropin alpha combination for the stimulation of follicular development in women with severe luteinizing hormone and follicle-stimulating hormone deficiency

Gonadotropin stimulation: past, present and future

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